The long-term objective of this proposal is to understand quantitatively the transduction mechanism in olfactory sensory neurons (OSNs). At present, there is hardly any biophysical information about each step in the transduction process. This information is crucial for truly understanding the process and ultimately its disease states, as amply exemplified in the advancements in our knowledge about retinal phototransduction in the past two decades. The specific aims are: 1) To examine the interaction between the odorant and the receptor protein, and to find out whether odorant receptors have any constitutive activity in the absence of odorants. 2) To understand the nature of the unitary event underlying the macroscopic olfactory response, and to see whether the response of an OSN to a single odorant molecule is indeed detectable. We shall also dissect the contributions of the cyclic nucleotide-gated current and the Ca-activated CI current to the unitary response. 3) To quantify Ca-dependent adaptation of the olfactory transduction process, and 4) To study Ca-independent adaptation of the process, and the possible roles of GRK3, RGS2 and phosducin in the termination of the olfactory response. The experimental approach involves recording from single OSNs from frog and mouse with a suction pipette. Genetically engineered mouse lines will also be used.